Graduate Student Presentations Day 3 - L. Amber Wilcox-O\'Hearn Sleep and Metabolism The Effects of Fasting PDF

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Graduate Student Presentations Day 3 - L. Amber WilcoxO'Hearn: Sleep and Metabolism: The Effects of Fasting Thursday, April 29, 2021

08:33

Stages of Fasting • Successive depletion: ○ Glycogen -> adaptation ○ Fat stores -> steady state, even fit individuals have weeks' worth of calories from fat reserves -> ketogenic diet ○ Lean mass -> starvation • Fasting acutely increases SWS and reduces REM and increases NREM ○ SWS in fasting depends on fasting phase ▪ A prior diet high in glycerol: 2x fasting tolerance & increased SWS until protein catabolism began ▪ When burning fat reserves, SWS goes up ▪ When burning lean mass, SWS goes down Species Differences • Humans, geese, emperor penguins: SWS increases • Mice, lean rats: SWS decreased • Hypothesizes: difference related to "fasting tolerance" (i.e. whether the animal is using fat or lean mass for energy)

Potential Biochemical Mechanisms • Central injection of acetoacetate (the primary ketone body), increased SWA and slightly reduced REM • Cortical injections of BDNF increased NREM Some Proposed Functions of Sleep • Energy conservation • Clearance of metabolites and oxidative stress • Synaptic pruning/homeostasis Expensive Tissue • Brains are energetically expensive -> ~20% energy • Clearance of metabolites and oxidative stress: immune/anti-oxidation response considered energetically costly • Synaptic pruning: synapses are costly Connections Between Energy and Sleep • Orexin ○ Increases and stabilizes wakefulness ○ Increased by fasting, low glucose ○ Ketogenic diet may help EDS in narcolepsy -> many limitations and can't restore orexin levels • Adenosine ○ Proposed mechanism of sleep homeostasis -> accumulated during wake; dissipates during sleep; associates with SWA ○ Reflects ATP breakdown, neuronal energy use ○ Fasting/ketogenic diets increases adenosine -> thought to have a causal role in ketogenic treatment of epilepsy and, maybe, in part, via improved sleep

Enhancing SWA May Improve Cognition Sleep Intensity and Cognition • Investigating the hypothesis that enhancing SWA could improve neurocognitive function • Cognitive function is associated with high-amplitude SWA • Insufficient NREM may be implicated in cognitive deficits Preliminary Evidence KDs Improve Cognition • Meta-study on KD for Alzheimer's ○ Most published articles showed a significant improvement of cognitive outcomes with ketone supplementation, regardless of the severity of cognitive impairments previously detected • Meta-study on KD for cognition in neurological diseases ○ Studies confirmed the effectiveness of the ketogenic diet in improving cognitive symptomatology - could be mediated by improvements in SWA...